Brachypodium distachyon, as an effective model of cereal grains, is susceptible to most destructive cereal pathogens. Senescence associated gene 101 (SAG101) has been studied extensively in Arabidopsis. SAG101 is one of the important regulators of plant immunity. However, no homologous genes of AtSAG101 were found in B. distachyon. In this study, the AtSAG101 gene was transformed into B. distachyon. Three transgenic plant lines containing the AtSAG101 gene were confirmed by PCR and GUS gene activity. There were fewer Puccinia brachypodii urediospores in the AtSAG101-overexpressing plants compared to wild type plants. P. brachypodii biomass was obviously decreased in AtSAG101 transgenic plants. The length of infection hyphae and infection unit areas of P. brachypodii were significantly limited in transgenic plants. Moreover, there were small lesions in AtSAG101 transgenic plants challenged by Magnaporthe oryzae. Salicylic acid accumulation was significantly increased, which led to elevated pathogenesis-related gene expression in transgenic B. distachyon inoculated by P. brachypodii or M. oryzae compared to wild type plants. These results were consistent with infected phenotypes. Overexpression of AtSAG101 in B. distachyon caused resistance to M. oryzae and P. brachypodii. These results suggest that AtSAG101 could regulate plant resistance in B. distachyon.